Pulmonary fibrosis is a disease in which lung tissues are fibrosed by accumulation of excess collagen and other cell matrices. Among the pulmonary fibrosis, idiopathic pulmonary fibrosis is a chronic intractable disease with a median survival time of 3 years on average, and five-year survival rate of 20 to 40%.
Acute lung injury is one kind of acute respiratory disturbances, and is acute respiratory failure showing pulmonary infiltrative shadow. The pathology of acute lung injury is pulmonary edema due to permeability promotion caused by pulmonary capillary endothelial cell and alveolar wall cell damage. The interstitial pulmonary edema, pulmonary alveolar edema and pulmonary collapse increase dead space ventilation ratio and develop hypoxemia.
As the situation stands, an effective treatment method is not available for pulmonary fibrosis and acute lung injury, and the development of an effective therapeutic drug has been desired. It has been reported that the onset of pulmonary fibrosis and acute lung injury involves expression of TGF-β1, and therefore, attempts have been made to inhibit gene expression (patent documents 1-5, non-patent documents 1-6).
As a technique for inhibiting gene expression, for example, RNA interference (RNAi) is known. Inhibition of gene expression by RNA interference is generally carried out, for example, by administering a short double-stranded RNA molecule to a cell or the like. The aforementioned double-stranded RNA molecule is generally called siRNA (small interfering RNA). As regards the aforementioned expression of TGF-β1 gene, siRNA has been studied; however, provision of a more effective nucleic acid molecule has been desired.
In recent years, the present inventors have newly found a more effective single-stranded nucleic acid molecule replacing siRNA (patent documents 6, 7, non-patent document 7).